Once the probes were fully advanced into the brain, we observed a decline in the compression force over time.

However, the compression force never decreased to zero.

This may indicate that chronically implanted probes experience a constant compression force when inserted in the brain, which may push the probe out of the brain over time if there is nothing to keep it in a fixed position.

Yet ... the Utah probe seems fine, up to many months in humans.

This may be a drawback for flexible probes [24], [25]. The approach to reduce tissue damage by reducing micromotion by not tethering the probe to the skull can also have this disadvantage [26]. Furthermore, the upward movement may lead to the inability of the contacts to record signals from the same neurons over long periods of time.

We did not observe a difference in initial insertion force, amount of dimpling, or the rest force after a 3-min rest period, but the force at the end of the insertion was significantly higher when inserting at 100 μm/s compared to 10 μm/s.

No significant difference in histological response observed between the two speeds.

(Interesting): eight identical electrode arrays implanted into the same region of different animals have shown that half the arrays continue to record neural signals for >14 weeks while in the other half of the arrays, single-unit yield rapidly degraded and ultimately failed over the same timescale.

In another study, aimed at uncovering the time course of insertion-related bleeding and coagulation, electrodes were implanted into the cortex of rats at varying time intervals (−120, −90, −60, −30, −15, and 0 min) using a micromanipulator and linear motor with an insertion speed of 2 mm/s.40 The results showed dramatic variability in BBB leakage that washed out any trend (Figure 3), suggesting that a separate underlying cause was responsible for the large inter- and intra-animal variability.

Author's opinion that this is due to carbon-carbon crosslink leading to mechanical toughening (hmm, evidence?)

Quote: since the PE formulation studied here was low-weight, it was expected to lose crystallinity upon cyclic flexing; high density PE's have in fact been observed to become more crystalline with working.

Very interesting, kinda like copper. This could definitely be put to good use.

Low density polyethylene has greater chain branching and entanglement than high-density resins; when stressed the crystallites are diminished in total bulk, degrading tensile properties ... for high-density resins, mechanical working loosens up the structure enough to allow new crystallization to exceed stress-induced shrinkage of crystallites; hence, the crystallinity increases.

Though this is a brief Nature intro article, I found it to be more usefully clear than the wikipedia articles on super-resolution techniques.

STORM and PALM seek to stochastically switch fluorophores between emission and dark states, and are parallel but stochastic; STED and RESOLFT use high-intensity donut beams to stimulate emission (STED) or photobleach (RESOLFT) fluorophores outside of an arbitrarily-small location.

All need gaussian-fitting to estimate emitter location from the point-spread function.

This article comments on a clever way of making 1e5 donuts for parallel (as opposed to rastered) STED / RESOLFT.

I doubt stetting up a STED microscope is at all easy; to get these resolutions, everything must be still to a few nm!

Atomic layer deposited (ALD) alumina is an excellent moisture barrier with WVTR at the order of ~ 10e-10 g·mm/m2·day [10-13]. But alumina alone is not suitable for encapsulation since it dissolves in water [14].

Demonstrated stable power-up of RF encapsulated devices for up to 600 equivalent days in 37C PBS.

One of the goals/needs of the lab is to be able to stimluate and record nervous tissue at the same time. We do not have immediate access to optogenetic methods, but what about lower frequency EM stimulation? The idea: if you put the stimulation frequency outside the recording system bandwidth, there is no need to switch, and indeed no reason you can't stimulate and record at the same time.

Hence, I very briefly checked for the effects of RF stimulation on nervous tissue.

shows that neurons are activated by pulsed RF, albeit through c-Fos staining. Electrodes were much larger in this study.

Also see PMID-15618777[3]associated editorial which calls for more extensive clinical, controlled testing. The editorial gives some very interesting personal details - scientists from the former Soviet bloc!

PMID-16310722[4]Pulsed radiofrequency applied to dorsal root ganglia causes a selective increase in ATF3 in small neurons.

used 20ms pulses of 500kHz.

Small diameter fibers are differentially activated.

Pulsed RF induces activating transcription factor 3 (ATF3), which has been used as an indicator of cellular stress in a variety of tissues.

However, there were no particular signs of axonal damage; hence the clinically effective analgesia may be reflective of a decrease in cell activity, synaptic release (or general cell health?)

Implies that RF may be dangerous below levels that cause tissue heating.

The consistency of leakage current suggests that no obvious corrosion was occurring to the Al2O3 film. The extremely low leakage current (≤20 pA) was excellent for IDEs after roughly three years of equivalent soaking time at 37 °C.

Still, they warn that it may not work as well for in-vivo devices, which are subject to tethering forces and micromotion.

Diffusion occurred during the curing process of the second layer and was controlled by the cure schedule.

It was found that a large diffusion distance, at least 200 nm, was required to obtain a bond whose strength was equal to that of bulk material.

Good protocol:

Dry first layer at 80C for 30 minutes.

150C (or lower?) bake of first layer. "as the polyamic acid imidizes (and the solvent is lost) its diffusive mobility decreases rapidly; very little diffusion occurs after the first few minutes of the second bake.

Spin coat second layer.

400C second bake.

Ductility is increased for polyimide that has experienced a series of increasing cure temperatures.

In this context it is worth noting that the contour length of a PMDA-ODA of 30,000 molecular weight is about 130nm, a value very similar to the diffusion distances measured when T1 (first layer bake) was 150C.

Parylene samples were subjected to accelerated lifetime testing (85 % relative humidity (RH) and 85 ̊C) for 20 days, and the film did not show appearance changes as observed by optical microscopy. However, X-ray diffractograms show that the film crystallinity increased during this test.

Wikipedia: Free iron is toxic to cells as it acts as a catalyst in the formation of free radicals from reactive oxygen species via the Fenton Reaction.[11] Hence vertebrates use an elaborate set of protective mechanisms to bind iron in various tissue compartments.

Interestingly, during the first few hours after implantation many microglial cells are undergoing cytoplasmic fragmentation (cytorrhexis) which indicates ongoing degeneration of these cells as their cytoplasm literally breaks apart. Cytorrhexis has been previously observed in the aged human brain where it becomes particular prominent in subjects with Alzheimer’s disease.

Could not discriminate abiotic (insulation, recording site size) and biotic (inflammatory response) causes of failure.

The important result is that materials with low protein-binding (e.g. alginate) have fewer bound microglia, hence better biocompatibility. It also seems to help if the material is highly hydrophilic.

Yes alginate is made from algae.

Used Michigan probes for implantation.

ED1 = pan-macrophage marker.

(quote:) Quantification of cells on the surface indicated that the number of adherent microglia appeared higher on the smooth side of the electrode compared to the grooved, recording site side (Fig. 2B), and declined with time. However, at no point were electrodes completely free of attached and activated microglial cells nor did these cells disappear from the interfacial zone along the electrode tract.

We have developed an ex vivo preparation to capture real-time images of tissue deformation during device insertion using thick tissue slices from rat brains prepared with fluorescently labeled vasculature.

Direct damage to the vasculature included severing, rupturing and dragging, and was often observed several hundred micrometers from the insertion site. (yikes!)

(!!!) wires are stiffened for implantation by temporarily attaching them to a micropipette guide with sucrose which subsequently dissolves in the brain!

the smooth sucrose (40 grams in 50ml of water heated to 118C) coating requires about a week of desiccation to become hard enough for insertion into the brain without premature softening. Sucrose becomes clear like glass once fully desiccated.

the air above the craniotomy is sufficiently humid to dissolve the sucrose if left there for more than a few seconds.

used a miniature single-channel FET amplifier as a headstage - only one channel out of 6 could be recorded at once :( Thus their reults only apply to the best of the microwires implanted - not to all of them.

recorded onto a mac quadra (hahah) 20khz 12 bit

applying 160ua microstimulation pulses can restore low (200kohm) electrode impedance. Recording quality was generally improved for a few days following stimulation but then returned to an asymptotic level with the impedance at approximately 900kOhm.

electrodes only seemed to last 5 weeks, whence they declined to about 27% yeild - see figure 8.

We studied the chronic brain foreign body response to planar solid silicon microelectrode arrays and planar lattice arrays with identical penetrating profiles but with reduced surface area in rats after an 8-week indwelling period.

Using quantitative immunohistochemistry, we found that presenting less surface area after equivalent iatrogenic injury is accompanied by significantly less

persistent macrophage activation,

decreased blood brain barrier leakiness,

and reduced neuronal cell loss.

Could be a factor of micromotion, too -- the lattice array has more anchoring points (?)

They propose it's a factor of TNF-α concentration around the implants. This, and other proinflammatory and cytoxic cytokines, is released by macrophages.

"Recent studies from our lab have described disruption of BBB integrity, indicated by the presence of autologous IgG in the brain parenchyma, surrounding both microwire and planar silicon recording devices ([1][2]. Under normal conditions, autologous IgG is excluded from the brain parenchyma (Azzi et al., 1990; Seitz et al., 1985) but has been observed following BBB disruption (Aihara et al., 1994).

E.g. the presence of IgG proves that the BBB was compromised.

Less so with the lattice implants.

Previous work from our lab using single microwires and single shaft, planar silicon microelectrode arrays indicated that the spatial distribution of GFAP does not increase with time over the indwelling period and did not support the “increase in astrogliosis over time hypothesis” as a dominant or general biologically related failure mechanism for this type of microelectrode recording device {1197}.

Important point: ED1 up-regulation and neuronal loss were not observed in microelectrode stab controls, indicating that the phenotype did not result from the initial mechanical trauma of electrode implantation, but was associated with the foreign body response.

Only tested response 2 and 4 weeks after implantation. Makes sense for stab wound, but didn't the want to see a longer term response? Or do their electrodes just not last that long?

What did they coat the silicon probes in?

Used silastic to shock-mount their floating electrodes, but this apparently made no difference compared to conventional dental cement and bone screw mounting.

Suggest that chronic inflammatory response may be related to the absorption of fibrogen and complement to the surface of the device (device should not be porous?), the subsequent release of pro-inflammatory and cytotoxic cytokines by activated microphages, and the persistence of activated macrophages around materials which cannot be broken down.

Well then, how do you make the electrodes biochemically / biologically 'invisible'?

Persistently activated microglia are found around insoluble plaques in AD (plaques that cannot be / are not removed from the brain via proteolysis. Microglia form 'glitter cells' when they engulf undigestible stubstances). This has been termed 'frustrated phagocytosis', which results in increased secretion of proinflamatory cytokines that directly or indirectly cause neuronal death.

Significant reductions in neurofiliament reactivity was seen up to 230um from the microelectrode interface; this was not seen for stab wounds. Maximum recording distance is about 130um; 100um more reasonable in normal conditions.

Accumulating evidence from postmortem analysis of patients implanted with DBS electrodes reveals that chronic neuroinflamation is part of the response to such (duller, larger) implants as well. They have seen cell loss up to 1mm fromt the electrode surface here.

PMID-13429398[0]Histopathological changes produced by implanted electrodes in cat brains; comparison with histopathological changes in human and experimental puncture wounds.

Quite a good and overcomplete / long article -- fully describes their result of implanting bundles of 0.005" varnished steel wires into the brains of cats.

Saw hemorrhagic necrosis, necrosis from edema, and eventual encapsulation and collapse of capilaries around the chronic implant. All things that we still have to contend with.

From [1]: ... For single penetrating electrodes into cat cortex, Collias and Manuelidis noted and increase in hemorrhagic damage near electrode tracks of the cortex nearest the point of electrode entry into the pia.

They also reported that the damage appeared to be randomly distributed among the implants, which they attributed to differences in local vasculature.

The toxicity of certain metals, namely, platinum, platinum-8% tungsten, platinum-10% rhodium, platinum-10% iridium, platinum-10% nickel, platinized platinum, a gold-nickel-chromium alloy, a gold-palladium-rhodium alloy, a chromium-nickel-molybdenum alloy (Vitallium), stainless steel, silver, rhenium, and gold, was evaluated histologically following chronic implantation for 2 months in the brains of cats. Of the above metals, all but silver were found to be nontoxic. Boron was also evaluated and found to be nontoxic.

STN-HFS-induced forelimb dyskinesia was blocked by microinjection of the Glu receptor antagonist kynurenate into the SNr and facilitated by microinjection of a mixture of the Glu receptor agonists AMPA and NMDA into the SNr.

Well, that just makes sense. STN is excitatory, GPi is an output structure of the BG, and stimulation should activate the area.

this is a good anatomy article, very descriptive -- almost too much information to grapple with.

STN = important structure for the modulation of activity of basal ganglia structures

STN is anterior-adjacent to the red nucleus

The average number of neurons in each STN nucleus varies from species to species and has been estimated to be ~25 000 in rats, 35 000 in marmosets, 155 000 in macaques, 230 000 in baboons and 560 000 in humans

The volume of the STN is ~0.8 mm3 in rats, 2.7 mm3 in marmosets, 34 mm3 in macaques, 50 mm3 in baboons and 240 mm3 in humans.

Deep Brain stimulation improves mobility/dexterity and dyskinesia of patients in general, via an increase in rate and decrease in reaction time, but it does not let the patient match force output to the object being manipulated (that is, the force is too large).

The excessive levels of grip force present in the stimulation 'off' state, and present from the early stages of the disease, however, were even more marked with STN stimulation on.

STN DBS may worsen the ability to match force characteristics to task requirements. (position control is improved?).

quite fascinating.

See also PMID-19266149[1]Distal and proximal prehension is differentially affected by Parkinson‘s disease The effect of conscious and subconscious load cues

asked PD and control patients to lift heavy and light objects.

While controls were able to normalize lift velocity with the help of both conscious and subconscious load cues, the PD patients could use neither form of cue, and retained a pathological overshoot in lift velocity.

Hence force control is remarkably affected in PD, which is consistent with the piper rhythm being absent / usually present for isometric contraction.

stroke of the STN results in hemiballismus - wild movements of the limbs. recall the input to the STN is inhibitory from GPe, and the output is exitatory to the GPi. chemical treatment is via dopamine blockade (1976!)

hemiballism is rare, but usually associated with lesion to the contralateral STN.

however, half the cases of hemiballismus are associated with damage to the afferent or efferent pathways to the STN.

I wish i could remember where i got these notes from, so as to verify the somewhat controversial statements. I found them written on the back of a piece of scrap paper.

neurophysiological recordings in animals show that over half of basal ganglia neurons fire in response to motor activity but none are triggered by passive limb movement.

in parkinson's disease (PD), the substantia nigra actually becomes pale to the eye.

stimulation of the striatum does not result in low-threshold movements like stimulation of the cortex does.

palladium does not seem linked to motor planning. (just execution?)

stimulation of the caudate causes movement, i.e. head turning, while stimulation of the ventromedial caudate produces arrest and crouching movements. (Delgado etc)

large bilateral striatal leasions cause inattention.

striatal units appear to signal movement, not generate/compute it (really?)

in parkinson's disease, motor learning appears normal - it is the initial slowness that is abnormal :: PD relates to the quality of movement, not the quality of the motor commands. Thus, perhaps PD is a disease of gating/attention?

in PD, all reflexes except the Hoffman-reflex appear normal.

The primary difference between the H-reflex and the spinal stretch reflex is that the H-reflex bypasses the muscle spindle and, therefore, is a valuable tool in assessing modulation of monosynaptic reflex activity in the spinal cord. The H-reflex is an estimate of alpha motoneuron (alphaMN) excitability when presynaptic inhibition and intrinsic excitability of the alphaMNs remain constant.

A lesion of the PPN (pedunculo pontine nucleus) was shown to restore decreased activity levels in the SNr and STN of a rat model of parkinson's (lesion of the SNc) PMID-17042796

From my reading, it seems that the diameter of these nanoparticles is important, but the grid spacing is not.

These nanoparticles strongly scatter light, and the degree of scattering is dependent on the local index of refraction + electric field.

The change in scattering due to applied electric field is very small, though - ~ 3e-6 1/V in the air-capacitor setup, ~1e-3 in solution when stimluated by cultured hippocampal neurons.

Noteably, nanoparticles are not diffraction limited - their measurement resolution is proportional to their size. Compare with voltage-sensitive dyes, which have a similar measurement signal-to-noise ratio, are diffraction limited, may be toxic, and may photobleach.

looks like the monkey can track the target firing rate rather accurately. "the output of cortical cells can provide information output rates moderately less precise than the intact motor system. "

Monkey can also activated sequences of neurons: A, then AB, then B.

people have also tried conditioning individual EMG units; it is sometimes possible to control 2 different motor units in the same muscle independently, but in general only a single channel of information can be obtained from one muscle, and gross EMGs are fine for this.

Thus surface EMG is preferred.

you can get ~ 2.73 bits/sec with gross EMG on a human; 2.99 bits/sec (max) with a monkey.

they remind us, of course, that an enormous amount of work remains to be done.

____References____

[0] Schmidt EM, Single neuron recording from motor cortex as a possible source of signals for control of external devices.Ann Biomed Eng 8:4-6, 339-49 (1980)

No PMID / bibtex penfield-1937. Somatic motor and sensory representation in the cerebral cortex of man as studied by electrical stimulation

Fritsch and Hitzig (1870) [0] cited as the first paper in electrical excitation of the CNS.

Good review of the scientific experiments thereafter, including stimulation to S1 by Ferrier, work with apes etc.

Central sulcus called the 'Rolandic fissure'.

Interesting! quote:

The account of Bartholow
(1874) is interesting to say the least and may be cited. His patient was a 30-year old-domestic. As an infant this unfortunate had chanced to fall into the fire, burning her scalp so badly that " hair was never reproduced." A piece of whale bone in the wig she was forced to wear irritated the scarred scalp and, by her statement, three months before she was admitted, an ulcer appeared. When she presented herself for relief, this had eroded the skull over a space 2 in. in diameter " where the pulsations of the brain are plainly seen."
Although " rather feeble-minded " Bartholow observed that Mary returned replies to all questions and no sensory or motor loss could be made out in spite of the fact that brain substance apparently had been injured in the process of evacuation of pus from the infected area. The doctor believed, therefore, that fine insulated needles could be introduced without further damage.

While the electrodes were in the right side Bartholow decided to try the effect of more current. ' Her countenance exhibited great distress and she began to cry. Very soon the left hand was extended as if in the act of taking hold of some object in front of her; the arm presently was agitated with clonic spasms ; her eyes became fixed with pupils widely dilated ; the lips were blue and she frothed at the mouth ; her breathing became stertorous, she lost conscious-ness and was violently convulsed on the left side. This convulsion lasted for five minutes and was succeeded by coma. She returned to consciousness in twenty minutes from the beginning of the attack and complained of some weakness and vertigo." Three days after this stimulation, following a series
of right-sided seizures, the patient died.

"Is it conceivable that behavior or the psyche can be related to electronics? Before answering these questions, we should ask one more: what is the main difference between primitive tribesmen still living in the jungle and the civilized human beings so well represented by this audience?" Education.

Kinda a ramble saying how education and understanding the brain is essential to our future.

Against atomic deterrence, unsurprisingly.

We are in the precarious race between the acquisition of many megatons of destructive power and the development of intelligent human beings who will make wise use of the forces at our disposal"

Radio receiver on a belt.

Elicited very complex movements from stimulating the thalamus, including walking from one side of the cage to the other, including avoiding the boss monkey!

He calls this 'electrical stimulation of the will'.

stimulate nucleus postero-ventralis induces targeted, well-directed attacks against other males of the group.

Stimulation of the caudate-septal lobes, just behind the frontal lobes, causes the boss monkey to become tame / tolerant / less aggressive.

When this function was enabled by pressing a button in the monkeys cage, the monkey most harrassed learned to press the button to halt the boss's aggressive behavior.

Regarding patients: "some of these patients have undergone testing for weeks or months, and lead a nearly normal life wthile 10, 20 or even more fine wires were present, in different cerebral areas and ready for stimulation from outside the scalp."

For example, in one patient, who spike a mean of 8.5 words per minute, by means of stimulation to the second temporal column increased his conversation to 44 words per minute." Menwhile, the number of friendly remarks increased by a factor of 9.

"Knowledge of the human mind may be decisive for our pursuit of happiness and for the very existence of mankind"

movements were seprarated based on speed analysis - that is, all the data were analyzed as discrete segments.

neurons were inactive during periods of hand stasis between movements.

tested the diversity of their training set in a clever way: they simulated neurons tuned to various parameters of the motion, and tested to see if their analysis could recover the tuning. it could.

however, they still used unvalidated regression analysis to test their hypothesis. regression analysis estimates how much variance is estimated by the cosine-tuning model - it returns an R^2.

either averaged the neuronal tuning over an entire movement or smoothed the firing rate using a 10hz upper cutoff.

Moran & Schwartz' old result seems to be as much a consequence of averaging across trials as it is a consequence of actual tuning...

whithout the averaging, only 3% of the variance could be attributed to speed tuning.

i think that they have a good point in all of this: when you eliminate sources of variance (e.g. starting position) from the behavior, either by mechanical restraint or simple omission of segments or even better averaging over trials, you will get a higher R^2. but it may be false, a compression of the space along an axis where they are not well correlated!

a model in which the final position matters little, but the velocity used to get there does, has been found to account for little of the neuronal variance.

instead, neurons are tuned to any of a number of movements that terminate near a preferred direction.

observational studies of of the normal psontaneous behavior of monkeys indicate that a high proportion of time is spent using the arm as a postural device.

therefore, they expect that neurons are tuned to endpoint posture.

modeled the neuronal firing as a gaussian surface in the 8-dimensional space of the arm posture.

in comparison to other studies, the offset between neural activity and behavior was not significantly different, over the entire population of recorded neurons, from zero. This may be due to the nature of the task, which was spontaneous and ongoing, not cue and reaction based, as in many other studies.

quote: This result suggests that the neuronal tuning to posture reflects reatively more and anticipation of the future state of the limb rather than a feedback signal about a recent state of the limb.

the responses of a substantial fraction of neurons in the primary visual cortex evolve from those that relate solely to the physical attributes of the stimuli to those that accurately predict the timing of reward.. wow!

rats. they put goggles on the rats to deliver full-fields retinal illumination for 400ms (isn't this cheating? full field?)

recorded from deep layers of V1

sensory processing does not seem to be reliable, stable, and reproducible...

rewarded only half of the trials, to see if the plasticity was a result of reward delivery or association of stimuli and reward.

after 5-7 sessions of training, neurons began to respond to the poststimulus reward time.

this was actually independent of reward delivery - only dependent on the time.

reward-related activity was only driven by the dominant eye.

individual neurons predict reward time quite accurately. (wha?)

responses continued even if the animal was no longer doing the task.

is this an artifact? of something else? what's going on? the suggest that it could be caused by subthreshold activity due to recurrent connections amplified by dopamine.

good background & review of surface EMG (sEMG) - noise levels, electrodes, electronics. eg. Instrumentation amplifiers with an input resistance < 100MOhm are not recommended, and the lower the input capacitance, the better: the impedance of a 10pf capacitor at 100hz is 160MOhm.

in primates, includes the medial caudate, which has been shown in fMRI to respond to reward prediction error. Neural activity in the caudate is attenuated when a monkey reaches optimal performance.

dorsal parts of the striatum (according to web: caudate, putamen, globus pallidus in primates) connect to the dorsal prefrontal and motor cortices

(according to them:) this corresponds to the putamen in primates. Activity in the putamen reflects performance but not learning.

activity in the putamen is highest after successful learning & accurate performance.

used muscimol (GABAa agonist, silences neural activity) and AP-5 (blocks NMDA based plasticity), in each of the target areas.

dorsal striatum is involved in performance but not learning

Injection of muscimol during acquisition did not impair test performance

Injection of muscimol during test phase did impair performance

Injection of AP-5 during acquisition had no effect.

in acquisition sessions, muscimol blocked instrumental response (performance); but muscimol only has a small effect when it was injected after rats perfected the task.

Idea: consistent behavior creates a stimulus-response association in extrastriatal brain areas, e.g. cerebral cortex. That is, the basal ganglia is the reinforcement signal, the cortex learns the association due to feedback-driven behavior? Not part of the habit system, but make and important contribution to goal-directed behavior.

This is consistent with the observation that behavior is initially goal driven but is later habitual.

Actually, other studies show that plasticity in the dorsal striatum may be detrimental to instrumental learning.

The number of neurons that fire just before the execution of a response is larger in the putamen than the caudate.

implanted bilater tripolar stimulating electrodes aimed at the lateral hypothalamus. These were tested for self-stimulation, and preferred locations/currents were selected for optimal ICS reinforcement.

Back projected stimuli onto a screen 50 cm from eye ; dot, bar, or small spot was effective in triggering patterned response, as with many of these studies.

For conditioning: set a threshold at the third quartile (1/4 of trials exceeded threshold); comparator circuit counted the number of spikes during stimulus presentation, and if threshold was exceeded, reinforcing ICS was delivered.

Reinforcing ICS started 300ms after visual stimulus and lasted 500ms.

Conditioning was deemed successful if the mean trial firing rate for the last 50 conditioned trials had a mean firing rate > 30% larger than the first 50 control trials.

While recording some cells, ICS reinforcement was delivered at random as control.

Conditioning produced changes within stimulus presentation but not outside.

They consider the use of an immobilized subject is a pro -- better control, rules out alternative explanations based on motor feedback.

In the heyday of prewar German scientific discovery, Foerster (3) established that electrical stimulation of the visual cortex in an awake patient during a neurosurgical intervention produced the percept of dots of light, called phosphenes, and that the location of a phosphene changed with that of the electrical stimulus.

people originally thought that loss of the photoreceptors would lead to degradation of the RGCs; this appears not to be true.

There is broad consensus that functional vision restoration is predicated on prior visual experience; this is different than cochlera prostheses, which work on congenitally deaf people.

Visual development depends on nearly a decade of high-resolution perception, and cannot be emulated later in life through a low-bw prosthesis.

There are at the present time at least 20 distinct research groups in at least 8 countries actively engaged in visual prosthesis development.

discuss a lot of pre-clinical testing & all the nitty-grity details, e.g. how to make a low res prosthesis work for reading.

An interesting field in ML is nonlinear dimensionality reduction - data may appear to be in a high-dimensional space, but mostly lies along a nonlinear lower-dimensional subspace or manifold. (Linear subspaces are easily discovered with PCA or SVD(*)). Dimensionality reduction projects high-dimensional data into a low-dimensional space with minimum information loss -> maximal reconstruction accuracy; nonlinear dim reduction does this (surprise!) using nonlinear mappings. These techniques set out to find the manifold(s):

Would be interesting to run nonlinear dimensionality reduction algorithms on our data! What sort of space does the motor system inhabit? Would it help with prediction? Am quite sure people have looked at Kohonen maps for this purpose.

Random irrelevant thought: I haven't been watching TV lately, but when I do, I find it difficult to recognize otherwise recognizable actors. In real life, I find no difficulty recognizing people, even some whom I don't know personally - is this a data thing (little training data), or mapping thing (not enough time training my TV-not-eyes facial recognition).

PMID-10404201 Real-time control of a robot arm using simultaneously recorded neurons in the motor cortex.

Abstract: To determine whether simultaneously recorded motor cortex neurons can be used for real-time device control, rats were trained to position a robot arm to obtain water by pressing a lever. Mathematical transformations, including neural networks, converted multineuron signals into 'neuronal population functions' that accurately predicted lever trajectory. Next, these functions were electronically converted into real-time signals for robot arm control. After switching to this 'neurorobotic' mode, 4 of 6 animals (those with > 25 task-related neurons) routinely used these brain-derived signals to position the robot arm and obtain water. With continued training in neurorobotic mode, the animals' lever movement diminished or stopped. These results suggest a possible means for movement restoration in paralysis patients.

The basic idea of the experiment. Rat controlled the water lever with a forelimb lever, then later learned to control the water lever directly. They used an artificial neural network to decode the intended movement.

Section 5.5 -- "Wait two minutes for the power resistor to cool before repeating step 5.4". (Might as well tell them why they are waiting, gives them more reason to do so).

Section 5.7 -- Remind the user to wait some time for the power resistors to cool before trying different power settings. At lower powers, they will not have to wait too long; higher power will require longer wait time. In the future might want to put a thermsistor/resettable poly fuse or the like in there to thermally protect the device. Or one of the bimetal heat switches that they use in hair dryers; I'd imagine that they are cheap.

I'm not very familiar with ESU devices, but is there a possibility to see varying power levels within the 4-second evaluation period? Would this be important to note?

For the assembly instructions:

Section 2.0 -- You can probably get some images of the resistors off digikey :-)

Also, don't need to number "2.x" all of the components. One number in that table should be enough.

Separate column for device quantity would aid clarity.

Section 3.0 -- Are numbers needed for this short list?

Section 4.0 -- Ditto. Maybe bullets would be clearer. As for the grounded bench, perhaps should explain that static electricity can damage the diodes.

Section 5.0 --

Why make the user refer to the appendix for the resistor color codes? Just take a picture of the finished board, with all but the resistors masked out or lightened in photoshop, so the assembler can see what goes where. Or some other clear figure.

Tools and materials should not get its own column; put that in a row or bullet before the table. Maybe have a bullet point: "Components needed: R8, R7, R6..." This lets you make the pictures larger.

Section 5.2 -- Figure 3 - exactly! good figure.

Might as well put the diode numbers and values in the table. There is enough space below the first instruction bullet point.

Section 5.3 - 5.6 -- looks good.

Section 5.7 -- I would have to try this; it seems that most of the creases are intuitively obvious. Again, don't see the need for the gray text, though. The figures are good & illustrative.

Section 5.9 -- Would it be easier to apply the labels before folding, that way it is easy to apply even and firm pressure? I'm extrapolating here, don't know.

Appendix A -- You can hold LEDs or other components flush by bending the leads out after insertion. Re-melting & pushing the leads in sometimes results in bad solder joints. Otherwise good.

PMID-17189946[0] Cortico-hippocampal interaction during up-down states and memory consolidation.

(from the associated review) Good pictorial description of how the hippocampus may impinge order upon the cortex:

During sleep the cortex is spontaneously and randomly active. Hippocampal activity is similarly disorganized.

During waking, the mouse/rat moves about in the environment, activating a sequence of place cells. The weights of the associated place cells are modified to reflect this sequence.

When the rat falls back to sleep, the hippocampus is still not random, and replays a compressed copy of the day's events to the cortex, which can then (and with other help, eg. ACh), learn/consolidate it.

PMID-17173043[0] Coordinated memory replay in the visual cortex and hippocampus during sleep.

EEG from Layer 5 of the visual cortex.

used tetrodes.

rats were trained to alternate loops in a figure-8 maze to get at food.

the walls of the maze were lined with high-contrast cues.

data for correlated activity between ctx and hippocampus weak - they just show that the frame ('up' period in cellular activity) start & end between the two regions are correlated. No surprise - they are in the same brain after all!

Found that cells in the deep visual cortex (V1 & V2) had localized firing fields. Rat vision is geared for navigation? (mostly?)

From this, they could show offline replay of the same sequence; these offline sequences were compressed by about 5-10.

task: two monkeys were trained to saccade to one of two targets, left/right pink/yellow. the choice was cued by the color of the central fixation target; when it changed, they should saccade to the same-colored target.

usually, the saccade direction remained the same; sometimes, it switched.

the switch could either occur to the same side as the SUA recording (ipsilateral) or to the opposite (contralateral).

found cells in the pre-SMA that would fire when the monkey had to change his adapted behavior

both cells that increased firing upon an ipsi-switch and contra-switch

Hypothesis: the creation and maintenance of psychotic or delusional beliefs is caused by (or causally related to) malfunction in the predictive error circuitry in the brain. (namely, the prefrontal cortex, substantia nigra, and striatum).

Previous studies have shown that administering Ketamine, a dissociative drug that can cause delusions, effects this same pathway.

The authors tested the hypothesis by training control and psychotic subjects in an associative task: subjects had to determine if a fictitious patient would be allergic to a meal given example meals and resulting allergic reaction.

Both sets had about the same behavioral performance; however, activation of the prefrontal cortex, substantia nigra, and left striatum was less in the psychotic (some drug treated) subjects. This comparison of activation was measured between control trials (no prediction error) and violation trials (prediction violated) as well as unovershadowing (a and b causes allergy, but a or b separately do not)

http://www.dana.org/news/cerebrum/detail.aspx?id=3066 -- great article, with a well thought out, delicate treatment of the ethical/moral/ legal issues created by the interaction between the biological roots of violence (or knowlege thereof) and legal / social systems. He posits that there must be a continuum between ratinoal free will and irrational, impulsive violent behavior, with people biased to both by genetics, development, traumatic head injury, and substance abuse (among others).

Quote: SuperMemo was like a genie that granted Wozniak a wish: unprecedented power to remember. But the value of what he remembered depended crucially on what he studied, and what he studied depended on his goals, and the selection of his goals rested upon the efficient acquisition of knowledge, in a regressive function that propelled him relentlessly along the path he had chosen.

the spinal cord is remarkably complex (of course, considering how old it is and how important it is for structuring movement and locomotion..well..most animals)

there is a lot of well-organized circuitry in the spinal cord mediating adaptive phenomena and reflexes like the clasp knife reflex (upper motoneuron disease where the resistance to flexion abruptly melts away when the joint is fully flexed)

PMID-16236777[0]Miniature neurologgers for flying pigeons: multichannel EEG and action and field potentials in combination with GPS recording.

Recording neuronal activity of animals moving through their natural habitat is difficult to achieve by means of conventional radiotelemetry. This illustration shows a new approach, exemplified by a homing pigeon carrying both a small GPS path recorder and a miniaturized action and field potential logger (“neurologger”), the entire assembly weighing maximally 35 g, a load carried easily by a pigeon over a distance of up to 50 km. Before release at a distant location, the devices are activated and store both positional and neuronal activity data during the entire flight. On return to the loft, all data are downloaded and can be analyzed using software for path analysis and electrical brain activity. Thus single unit activity or EEG patterns can be matched to the flight path superimposed on topographical maps. Such neurologgers may also be useful for a variety of studies using unrestrained laboratory animals in different environments or test apparatuses. The prototype on the hand-held pigeon records and stores EEG simultaneously from eight channels up to 47 h, or single unit activity from two channels during 9 h, but the number of channels can be increased without much gain in weight by sandwiching several of these devices. Further miniaturization can be expected. For details, see Vyssotski AL, Serkov AN, Itskov PM, Dell Omo G, Latanov AV, Wolfer DP, and Lipp H-P. Miniature neurologgers for flying pigeons: multichannel EEG and action and field potentials in combination with GPS recording. [1]

basal ganglia output is directed toward the ventral anterior, ventrolateral, and centromedial nuclei of the thalamus, which, in turn, project back to the cortex. Plus, the output of the basal ganglia project to the cortex.

spindle neurons are found in the insular cortex as well as the anterior cingulate cortex, but only, apparently, in great apes. Activity in the insular cortex has been found to be correlated to feeling empathy.

http://mattl.co.uk/apache2subversiondebianhowto.html pretty good. SSL and subversion seems to cause problems with apache2 on this 'unstable' Debian build - it complains of a BAD MAC header after a deterministic number of bytes are transmitted. Therefore I moved to port 80 from 443.

Pathformer is an electrosurgical hand-held meidcal device that cuts holes in nails and skin. It operates on mesoscissioning technology, cutting the nail/skin with a microcutting tool, using skin impedance as a feedback for stopping the cutting intervention.
Pathformer is approved by FDA for creating holes in nails for treating subungual hematoma (black toe).